Curcumin (Cur) is a principal curcuminoid of Curcuma longa, a member of the Zingiberaceae family. The plant is distributed throughout tropical and subtropical regions of the world, being widely cultivated in south and south-east Asian countries. Turmeric, i.e., the ground rhizomes of C. longa has been long used in food as a spice, and as a main colouring substance. Curcumin possesses several health endowing properties vis-a-vis, antioxidant, anti-inflammatory, anti-carcinogenic, chemo-preventive, anti-microbial and chemo-therapeutic properties. The manifold benefits of curcumin, however, are restricted by its low oral bioavailability, indicated by the rate and extent at which orally administered curcumin enters the systemic circulation and reaches target sites.
The vital factors influencing the bioavailability of a therapeutic molecule are solubilization, absorption, and metabolism. It is a known fact that curcumin is insoluble in aqueous solutions and requires a solvent system for its complete dissolution. Internally curcumin undergoes rapid metabolism in the human body therefore rendering the absorption rate of curcumin to remain elusive. A major portion of this compound remains unabsorbed due to a fairly low intestinal absorption capacity. Even the minor amount which is actually absorbed is rapidly metabolized in the liver and eliminated from the body by the gall bladder. Various studies have verified that even a very high oral dose of curcumin i.e. up to 1 g/kg−1 of the body weight is almost completely eliminated by the human metabolic system. In view of the limiting factors affecting the oral bioavailability of curcumin, it is necessary to devise mechanisms of solubilization and absorption, appropriate for developing formulations which are able to improve the solubilization and the oral bioavailability of curcumin.
Curcumin i.e. diferuloylmethane, a bright orange yellow pigment is the main active ingredient of turmeric. Curcumin exhibits tautomerism in its molecular structure and thus exists in the enol form in nonpolar solvents, because of intra-molecular hydrogen bond formation and in the di-keto form in polar solvents. The keto form of Curcumin acts as a proton donor in acidic and neutral media, whereas at pH values above 8 the enol form dominates and acts as an electron donor. The existence of the phenolic, beta-diketone, as well as the methoxy groups of Curcumin contribute to its free-radical scavenging property. This property imparts the anti-cancer character to this compound. However, these results have not been reflected well in clinical studies mainly due to the low oral bioavailability of Curcumin. Therefore, several soft material systems including liposomes, microspheres, dendrimers, micelles, hydrogels and solid lipid nanoscale particles have been explored to design specific drug-delivery systems for curcumin. These nano-assembly forming procedures designed to improve the bio-availability of curcumin are all inherently expensive and hence there is a strong urge to obtain cost-effective replacements for this system.
There are a few research studies that emphasize the use of nanotechnology based methods to enhance bioavailability of insoluble therapeutic molecules, one of them being curcumin. Hailong Yu and Qingrong Huang in J. Agric. Food Chem., 2012, 60 (21), 5373-79 discloses organogel-based nanoemulsions developed for oral delivery of curcumin and improvement of its bioavailability. The surfactant employed for the dissolution of curcumin therein was Tween 20, the solvent being known for its role in development and reproductive toxicity in animal studies. Also there have also been concerns raised of contamination of Tween 20 or polysorbate 20 with carcinogenic 1,4-dioxane. Therefore, the use of biocompatible environmentally friendly ingredients having absolutely no hazardous effects on human beings may be used in the development of nano-emulsion or micro-emulsion based formulations comprising curcumin.
Biosurfactants derived from microorganisms are an interesting category of bio-organic systems with potential applications in biomedical science. They can be produced from renewable feedstock or waste material by natural fermentation. These amphiphilic compounds are known to easily form self assemblies at different pH conditions in aqueous environment. Sophorolipids are an eco-friendly and biocompatible class of amphiphilic biosurfactants which easily form emulsions in aqueous solution to reduce the surf ace tension and interfacial energies. Sophorolipids possess unique structures that can be engineered to suit specific application domains. Sophorolipid exists in two forms—acidic and lactonic. Lactonic sophorolipids have revealed superior antimicrobial, antiviral, antifungal, anti-inflammatory and anticancer activity. In present invention we have applied acidic sophorolipid to enhanced curcumin solubility, bioavailability and as a carrier in drug delivery to treat cancer cell line. Acidic sophorolipids (SL(A)), are known to form micelles, which interact depending on the pH of the system. SL(A), is composed of a sophorose unit attached to an oleic acid moiety through an ether bond on the C17 carbon atom of the fatty acid chain. This particular characteristic leaves the —COOH group available and responsive to changes in pH of the solution giving rise to the possibility of a series of self-assembled structures.
In the light of the prior arts with regard to available expensive technologies in preparing various nano-systems in improving the bioavailability of curcumin, there is still a scope in the art to provide cost-effective and bioavailable curcumin compositions.